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Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA

Herein we present the algorithm and performance assessment of our newly developed conformer generator iCon that was implemented in LigandScout 4.0. Two data sets of high-quality X-ray structures of drug-like small molecules originating from the Protein Data Bank (200 ligands) and the Cambridge Struc...

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Autores principales: Poli, Giulio, Seidel, Thomas, Langer, Thierry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018197/
https://www.ncbi.nlm.nih.gov/pubmed/29971231
http://dx.doi.org/10.3389/fchem.2018.00229
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author Poli, Giulio
Seidel, Thomas
Langer, Thierry
author_facet Poli, Giulio
Seidel, Thomas
Langer, Thierry
author_sort Poli, Giulio
collection PubMed
description Herein we present the algorithm and performance assessment of our newly developed conformer generator iCon that was implemented in LigandScout 4.0. Two data sets of high-quality X-ray structures of drug-like small molecules originating from the Protein Data Bank (200 ligands) and the Cambridge Structural Database (481 molecules) were used to validate iCon's performance in the reproduction of experimental conformations. OpenEye's conformer generator OMEGA was subjected to the same evaluation and served as a reference software in this analysis. We tested several setting patterns in order to identify the most suitable and efficient ones for conformational sampling with iCon; equivalent settings were also tested on OMEGA in order to compare the results obtained from the two programs and better assess iCon's performance. Overall, this study proved that iCon is able to generate reliable representative conformational ensembles of drug-like small molecules, yielding results comparable to those showed by OMEGA, and thus is ready to serve as a valuable tool for computer-aided drug design.
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spelling pubmed-60181972018-07-03 Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA Poli, Giulio Seidel, Thomas Langer, Thierry Front Chem Chemistry Herein we present the algorithm and performance assessment of our newly developed conformer generator iCon that was implemented in LigandScout 4.0. Two data sets of high-quality X-ray structures of drug-like small molecules originating from the Protein Data Bank (200 ligands) and the Cambridge Structural Database (481 molecules) were used to validate iCon's performance in the reproduction of experimental conformations. OpenEye's conformer generator OMEGA was subjected to the same evaluation and served as a reference software in this analysis. We tested several setting patterns in order to identify the most suitable and efficient ones for conformational sampling with iCon; equivalent settings were also tested on OMEGA in order to compare the results obtained from the two programs and better assess iCon's performance. Overall, this study proved that iCon is able to generate reliable representative conformational ensembles of drug-like small molecules, yielding results comparable to those showed by OMEGA, and thus is ready to serve as a valuable tool for computer-aided drug design. Frontiers Media S.A. 2018-06-19 /pmc/articles/PMC6018197/ /pubmed/29971231 http://dx.doi.org/10.3389/fchem.2018.00229 Text en Copyright © 2018 Poli, Seidel and Langer. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Chemistry
Poli, Giulio
Seidel, Thomas
Langer, Thierry
Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title_full Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title_fullStr Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title_full_unstemmed Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title_short Conformational Sampling of Small Molecules With iCon: Performance Assessment in Comparison With OMEGA
title_sort conformational sampling of small molecules with icon: performance assessment in comparison with omega
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018197/
https://www.ncbi.nlm.nih.gov/pubmed/29971231
http://dx.doi.org/10.3389/fchem.2018.00229
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